Bottom Line:
A complete understanding of the relationship between the amino acid sequence and resulting protein function remains an open problem in the biophysical sciences.Mu-8 helps to identify areas of the protein that exhibit: (1) significantly different bio-chemical characteristics, (2) relative conservation in the family, and (3) proximity to other regions that have suspect behavior in the folded protein.We demonstrate Mu-8 in a case study with data provided by the 2013 BioVis contest.

Background: A complete understanding of the relationship between the amino acid sequence and resulting protein function remains an open problem in the biophysical sciences. Current approaches often rely on diagnosing functionally relevant mutations by determining whether an amino acid frequently occurs at a specific position within the protein family. However, these methods do not account for the biophysical properties and the 3D structure of the protein. We have developed an interactive visualization technique, Mu-8, that provides researchers with a holistic view of the differences of a selected protein with respect to a family of homologous proteins. Mu-8 helps to identify areas of the protein that exhibit: (1) significantly different bio-chemical characteristics, (2) relative conservation in the family, and (3) proximity to other regions that have suspect behavior in the folded protein.

Methods: Our approach quantifies and communicates the difference between a reference protein and its family based on amino acid indices or principal components of amino acid index classes, while accounting for conservation, proximity amongst residues, and overall 3D structure.

Results: We demonstrate Mu-8 in a case study with data provided by the 2013 BioVis contest. When comparing the sequence of a dysfunctional protein to its functional family, Mu-8 reveals several candidate regions that may cause function to break down.

Figure 4: The residues in the focus region are within the specified distance of three adjacent residues further down the sequence, as illustrated by the black arcs. To reduce visual clutter, we replace the arcs connecting individual residues with chords (shown in gray) that connect proximate regions.

Mentions:
It is natural that the immediate neighborhoods of a residue are at similar distances to other neighborhoods in the sequence. We use this observation to reduce the visual clutter of the chords by bundling regions with similar proximity, as illustrated in Figure 4. In this example, the two residues in the focus region (M and A) are all connected to three residues adjacent to each other (V, G, and G). Instead of rendering a chord for every residue, as shown in black, we bundle them to a wider arch, shown in gray.

Figure 4: The residues in the focus region are within the specified distance of three adjacent residues further down the sequence, as illustrated by the black arcs. To reduce visual clutter, we replace the arcs connecting individual residues with chords (shown in gray) that connect proximate regions.

Mentions:
It is natural that the immediate neighborhoods of a residue are at similar distances to other neighborhoods in the sequence. We use this observation to reduce the visual clutter of the chords by bundling regions with similar proximity, as illustrated in Figure 4. In this example, the two residues in the focus region (M and A) are all connected to three residues adjacent to each other (V, G, and G). Instead of rendering a chord for every residue, as shown in black, we bundle them to a wider arch, shown in gray.

Bottom Line:
A complete understanding of the relationship between the amino acid sequence and resulting protein function remains an open problem in the biophysical sciences.Mu-8 helps to identify areas of the protein that exhibit: (1) significantly different bio-chemical characteristics, (2) relative conservation in the family, and (3) proximity to other regions that have suspect behavior in the folded protein.We demonstrate Mu-8 in a case study with data provided by the 2013 BioVis contest.

Background: A complete understanding of the relationship between the amino acid sequence and resulting protein function remains an open problem in the biophysical sciences. Current approaches often rely on diagnosing functionally relevant mutations by determining whether an amino acid frequently occurs at a specific position within the protein family. However, these methods do not account for the biophysical properties and the 3D structure of the protein. We have developed an interactive visualization technique, Mu-8, that provides researchers with a holistic view of the differences of a selected protein with respect to a family of homologous proteins. Mu-8 helps to identify areas of the protein that exhibit: (1) significantly different bio-chemical characteristics, (2) relative conservation in the family, and (3) proximity to other regions that have suspect behavior in the folded protein.

Methods: Our approach quantifies and communicates the difference between a reference protein and its family based on amino acid indices or principal components of amino acid index classes, while accounting for conservation, proximity amongst residues, and overall 3D structure.

Results: We demonstrate Mu-8 in a case study with data provided by the 2013 BioVis contest. When comparing the sequence of a dysfunctional protein to its functional family, Mu-8 reveals several candidate regions that may cause function to break down.